Jonathan Powell

Fine and ultrafine particles of the diet: influence on the mucosal immune response and association with Crohn’s disease

Crohns disease is a modern Western disease characterised by transmural inflammation of the gastrointestinal tract. It is of unknown aetiology, but evidence suggests that it results from a combination of genetic predisposition and environmental factors. Bacterial-sized microparticles (0.1-1.0 microm) are potent adjuvants in model antigen-mediated immune responses and are increasingly associated with disease. Microparticles of TiO2 and aluminosilicate accumulate in macrophages of human gut-associated lymphoid tissue where the earliest signs of lesions in Crohns disease are observed. Dietary microparticles are of endogenous or exogenous origin. Endogenous microparticles dominate and are calcium phosphate (most probably hydroxyapatite), which precipitates in the lumen of the mid-distal gastrointestinal tract due to secretion of Ca and phosphate in the succus entericus. Exogenous dietary microparticles are contaminants (soil and/or dust) and food additives. TiO2, for example, is a food colourant, and aluminosilicates are anti-caking agents, although some aluminosilicates occur as natural contaminants. Food additives alone account for ingestion of approximately 10(12) particles/person per d. Possible mechanisms for the role of exogenous and endogenous dietary microparticles in promoting toleragenic or immune responses of gastrointestinal mucosal phagocytosis are discussed. In a double-blind randomised pilot study we have shown that a diet low in Ca and exogenous microparticles appears to alleviate the symptoms of ileal Crohns disease, with a significant (P= 0.002) improvement in the Crohns disease activity index. A multi-centre trial and further mechanistic studies at the cellular level are underway.

The effect of cocoa procyanidins on the transcription and secretion of interleukin 1β in peripheral blood mononuclear cells.

Recent data has demonstrated that cacao liquor polyphenols (procyanidins) have antioxidant activity, inhibit mRNA expression of interleukin-2 and are potent inhibitors of acute inflammation. Given the widespread ingestion of cocoa in many cultures, we investigated whether cocoa, in its isolated procyanidin fractions (monomer through decamer), would modulate synthesis of the pro-inflammatory cytokine, interleukin-1 beta. Both resting and phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) were investigated at the levels of transcription and protein secretion. Individual cocoa fractions were shown to augment constitutive IL-1 beta gene expression, although values varied between subjects. Interestingly, the smaller fractions of cocoa (monomer-tetramer) consistently reduced IL-1 beta expression of PHA-stimulated cells by 1-15%, while the larger oligomers (pentamer-decamer) increased expression by 4-52%. These data, observed at the transcription level, were reflected in protein levels in PHA-induced PBMC. The presence or absence of PHA did not alter the effects of the cocoa procyanidins with the exception of the pentamer. This study offers additional data for the consideration of the health-benefits of dietary polyphenols from a wide variety of foods, including those benefits associated specifically with cocoa and chocolate consumption.

Intake of dietary iron is low in patients with Crohn's disease: a case–control study

Patients with Crohns disease (CD) often experience Fe deficiency (ID) and frequently alter their diet to relieve abdominal symptoms. The present study set out to assess whether patients with CD have dietary habits that lead to low Fe intakes and/or reduced bioavailable Fe compared with control subjects. Patients with asymptomatic CD were matched to controls (n 91/group). Dietary intakes of Fe and contributions from different food groups were compared using a 7 d food diary. Promoters and inhibitors of non-haem Fe absorption were investigated and a recently published algorithm was applied to assess bioavailable Fe. Fewer patients than controls met the reference nutrient intake for Fe (32% CD patients v. 42% controls). Overall, patients had significantly lower mean Fe intakes (by 2.3 mg/d) and Fe density (by 0.26 mg/MJ (1.1 mg/1000 kcal)) compared with controls (both P<0.001). Differences were mainly due to a preference among CD patients for low-fibre non-Fe fortified cereals, particularly breakfast cereals. In particular, control subjects had higher Fe intakes than matched CD subjects for men (P<0.001) and women less than 50 years (P=0.03). Intakes of both ascorbic acid (P<0.001) and phytic acid (P<0.01), but not animal tissue (P=1.0), were lower in patients with CD, but these had no overall effect on the predicted percentage of bioavailable Fe. Thus total bioavailable Fe was reduced in patients with CD due to lower intakes (P<0.01). Dietary Fe intakes are low in CD patients, which may contribute to an increased risk of ID and anaemia. Changing dietary advice may compromise perceived symptoms of the disease so the need for Fe supplementation should be carefully considered.

Enrichment in trace metals (Al, Mn, Co, Cu, Mo, Cd, Fe, Zn, Pb and Hg) of macro-invertebrate habitats at hydrothermal vents along the Mid Atlantic Ridge

The present study describes several features of the aquatic environment with the emphasis on the total vs. filter-passing fraction (FP) of heavy metals in microhabitats of two typical deep-sea vent organisms: the filter-feeder, symbiont-bearing Bathymodiolus and the grazer shrimps Rimicaris/Mirocaris from the Mid-Atlantic Ridge (MAR). The concentration of 10 trace elements: Al, Mn, Co, Cu, Mo, Cd, Fe, Zn, Pb and Hg was explored highlighting common and distinctive features among the five hydrothermal vent sites of the MAR: Menez Gwen, Lucky Strike, Rainbow, Saldanha, and Menez Hom that are all geo-chemically different when looking at the undiluted hydrothermal fluid composition. The drop off in the percentage of FP from total metal concentration in mussel and/or shrimp inhabited water samples (in mussel beds at Rainbow, for instance, FP fraction of Fe was below 23%, Zn 24 %, Al 65%, Cu 70%, and Mn 89%) as compared to non-inhabited areas (where 94% of the Fe, 90% of the Zn, 100% of the other metals was in the FP fraction) may indicate an influence of vent organisms on their habitat’s chemistry, which in turn may determine adaptational strategies to elevated levels of toxic heavy metals. Predominance of particulate fraction over the soluble metals, jointly with the morphological structure and elemental composition of typical particles in these vent habitats suggest a more limited metal bioavailability to vent organisms as previously thought. In addition, it is evoked that vent invertebrates may have developed highly efficient metal-handling strategies targeting particulate phase of various metals present in the mixing zones that enables their survival under these extreme conditions.

Oral ferrous sulphate leads to a marked increase in pro‐oxidant nontransferrin‐bound iron

Sir, Serum nontransferrin-bound iron (NTBI) is a potential catalyst for the production of reactive oxygen species, contributing to tissue damage. Nontransferrin-bound iron not only occurs in iron overload but also during intravenous iron infusion, possibly owing to the rapid saturation of transferrin, as a result of a rapid influx of iron [1]. More recently, NTBI was found to be positively correlated with lipid peroxidation in Beta-Thalassaemia and haemodialysis patients [2,3], although the relationship between NTBI and oxidative damage in vivo is contentious. Nevertheless, the presence of NTBI may explain published reports of lipid peroxidation after oral FeSO 4 [4,5], and as this is the usual treatment for IDA the occurrence of pro-oxidant NTBI during FeSO 4 treatment could have serious clinical implications. Therefore, we aimed to determine whether oral FeSO 4 results in the formation of serum NTBI in anaemic women. Seven anaemic women (mean haemoglobin 111 ± 5 g L − 1 ; serum ferritin 11·4 ± 2 μ g L − 1 ) who were otherwise healthy and of childbearing age completed this study. All subjects were recruited from the student and staff population at Kings College London and were not taking any medications nor had any history of chronic illness including gastrointestinal disease, although the exact causes of anaemia were not investigated. After an overnight fast, subjects were administered a tablet containing 200 mg of FeSO 4 (65 mg of elemental iron; Alpharma, Barnstaple, UK), with two slices of toasted white bread, margarine, honey and dilute orange cordial (visit 1), or 200 mg of FeSO 4 with the same drink but without food (visit 2). The meal (including drink) was low in inhibitors of iron absorption and contained only a trace of vitamin C. Serial blood samples were taken through an indwelling venous catheter before and after oral iron for 4 h on both occasions. Blood was drawn into vacutainers without additives to determine total serum iron, total iron binding capacity (TIBC) and serum NTBI. Serum ferritin, full blood count, total serum iron and TIBC were measured using routine laboratory methods, and serum was prepared for NTBI analysis using a method described elsewhere [6] and analyzed using an iron-free high-performance liquid chromatography system. Transferrin saturation was calculated (serum iron × 100/TIBC), and the rate of iron absorption was estimated using a recently reported equation [7]. We used a repeated measures  to test the increase in total serum iron, NTBI and transferrin saturation following FeSO 4 , and a simple linear fit to evaluate the correlation between NTBI and iron absorption, and NTBI and transferrin saturation. Neither the increase in total serum iron nor NTBI differed significantly when FeSO 4 was taken with or without food (both P < 0·001; Fig. 1), probably because the meal was low in compounds that inhibit iron absorption and vitamin C levels were similarly low on both occasions. On both occasions, serum transferrin concentration was in the normal range and was similar at baseline and 210 min after 200 mg of FeSO 4 (visit 1: 2·65 ± 0·10 g L − 1 at 0 min vs. 2·67 ± 0·08 g L − 1 at 210 min; and visit 2: 2·71 ± 0·09 g L − 1 vs. 2·82 ± 0·08 g L − 1 ). However, transferrin saturation increased from baseline to 210 min post-FeSO 4 , in conjunction with an increase in serum NTBI (Fig. 2). The mean ( ± SE) peak increase in serum NTBI was 4·6 ± 0·5 μ mol L − 1 and 3·9 ± 1·1 μ mol L − 1 , following 200 mg of All authors contributed to the study concept, while C. Hutchinson designed the study and prepared the manuscript with contributions from C.A. Geissler, R.C. Hider and J.J. Powell. W. Al-Ashgar carried out the study under the supervision of C. Hutchinson, and D.Y. Liu analyzed serum samples for NTBI. All authors approved and contributed academically to the final manuscript.

UK Food Standards Agency Optimal Nutrition Status Workshop: environmental factors that affect bone health throughout life

The UK Food Standards Agency (FSA) convened a group of expert scientists to discuss and review UK FSA- and Department of Health-funded research on diet and bone health. This research focused on the lifestyle factors that are amenable to change and may significantly affect bone health and the risk of osteoporotic fracture. The potential benefits of fruits and vegetables, meat, Ca, vitamins D and K and phyto-oestrogens were presented and discussed. Other lifestyle factors were also discussed, particularly the effect of physical activity and possible gene-nutrient interactions affecting bone health.

AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers

Smoking cannabis daily doubles an individual’s risk of developing a psychotic disorder, yet indicators of specific vulnerability have proved largely elusive. Genetic variation is one potential risk modifier. Single-nucleotide polymorphisms in the AKT1 and catechol-O-methyltransferase (COMT) genes have been implicated in the interaction between cannabis, psychosis and cognition, but no studies have examined their impact on an individual’s acute response to smoked cannabis. A total 442 healthy young cannabis users were tested while intoxicated with their own cannabis—which was analysed for delta-9-tetrahydrocannbinol (THC) and cannabidiol content—and also ±7 days apart when drug-free. Psychotomimetic symptoms and working memory were assessed on both the sessions. Variation at the rs2494732 locus of the AKT1 gene predicted acute psychotic response to cannabis along with dependence on the drug and baseline schizotypal symptoms. Working memory following cannabis acutely was worse in females, with some suggestion of an impact of COMT polymorphism on working memory when drug-free. These findings are the first to demonstrate that AKT1 mediates the acute response to cannabis in otherwise healthy individuals and implicate the AKT1 pathway as a possible target for prevention and treatment of cannabis psychosis.

Rapid non-equilibrium aluminium-ligand interactions: studies on the precipitation of aluminium by laser light scattering, ultrafiltration and centrifugation.

The study aimed to develop simple assays to study aluminium-ligand interactions in natural/biological systems where equilibrium is rarely reached and thus where the initial seconds or hours of interactions are important. The immediate and non-equilibrium precipitation of aluminium hydroxide, in aqueous solution at neutral pH, was therefore studied by laser light scattering (diffraction), ultrafiltration and centrifugation. The interaction of weak ligands, present in the gastrointestinal lumen, on the precipitation of aluminium hydroxide was also investigated. The initial kinetics and particle sizes of precipitated aluminium hydroxide were sensitive to a number of external factors, including the presence of weak ligand (bicarbonate), sheer force (stirring), electrolyte concentration and initial (i.e. added) aluminium concentration. However, after a few seconds (no weak ligand), or several hundred seconds (with weak ligand), the subsequent observed changes to the solid phase were of small magnitude and occurred slowly. Thus, a 25-min window, within 5 and 30 min of pH adjustment, can be used to study the interactions of aluminium-ligand. This may approximate better to most natural systems where unperturbed aluminium-ligand equilibrium must rarely exist.

CMRA with 100% navigator efficiency with 3D self navigation and interleaved scanning

Background In recent years many novel self navigation techniques have been proposed to solve the problems associated with cardiac motion in coronary MR angiography (CMRA). A new method of interleaved scanning (iScan) allows more flexibility in designing and testing novel imaging sequences as independent scans, with different imaging parameters including k-space trajectories, can be interleaved. We compared the performance of a 3D self navigator (3DSN) with 100% scan efficiency to traditional 1D navigators, whereby the 3DSN scan was setup as a single shot scan and was called by the high resolution segmented multishot CMRA scan each cardiac cycle. We have shown in previous work that correcting all acquired data in foot-head (FH) and left-right direction (LR) can provide equivalent image quality to traditional gated scans (J Powell et al. 2013 Proc. ISMRM). Here we sought to investigate and compare the effect of correcting data in 3 dimensions (FH, LR and AP).

Influence of oligomeric silicic and humic acids on aluminum accumulation in a freshwater grazing invertebrate.

This study examined the influence of oligomeric silicic acid and humic acid on aluminum in the water column and its accumulation in the freshwater snail Lymnaea stagnalis. Forty-eight hours after addition of Al (500 microg L(-1)), 83% of the metal was lost from the water column. This loss was reduced by oligomeric silica (20 mg L(-1)) and by humic acid (10 mg L(-1)). Aluminum accumulated in the digestive gland and, to a lesser extent, in the remaining soft tissues, and this accumulation was reduced by oligomeric silica. In the presence of humic acid, Al accumulation in the digestive gland was unaffected, though less was accumulated in the remaining tissues. Snails accumulated Si preferentially in the digestive gland and this accumulation was increased in the presence of added Al. Thus, both oligomeric silica and humic acid influence Al bioavailability and Si is upregulated in the digestive gland in the presence of Al.